On-line desorption of dried blood spot: A novel approach for the direct LC/MS analysis of micro-whole blood samples.

The aim of this work is to present a new concept, called on-line desorption of dried blood spots (on-line DBS), allowing the direct analysis of a dried blood spot coupled to liquid chromatography mass spectrometry device (LC/MS). The system is based on an inox cell which can receive a blood sample (10 microL) previously spotted on a filter paper. The cell is then integrated into LC/MS system where the analytes are desorbed out of the paper towards a column switching system ensuring the purification and separation of the compounds before their detection on a single quadrupole MS coupled to atmospheric pressure chemical ionisation (APCI) source. The described procedure implies that no pretreatment is necessary in spite the analysis is based on whole blood sample. To ensure the applicability of the concept, saquinavir, imipramine, and verapamil were chosen. Despite the use of a small sampling volume and a single quadrupole detector, on-line DBS allowed the analyses of these three compounds over their therapeutic concentrations from 50 to 500 ng/mL for imipramine and verapamil and from 100 to 1000 ng/mL for saquinavir. Moreover, the method showed good repeatability with relative standard deviation (RSD) lower than 15% based on two levels of concentration (low and high). Function responses were found to be linear over the therapeutic concentration for each compound and were used to determine the concentrations of real patient samples for saquinavir. Comparison of the founded values with those of a validated method used routinely in a reference laboratory showed a good correlation between the two methods. Moreover, good selectivity was observed ensuring that no endogenous or chemical components interfered with the quantitation of the analytes. This work demonstrates the feasibility and applicability of the on-line DBS procedure for bioanalysis.

Studies on underwater propagation development of programmable arrays

The thesis presented here includes the designing of underwater transducer arrays, taking into account the ‘interaction effects’ [30] among the closely packed radiators. Methods of minimizing the ‘interaction effects‘ by modifying the radiating aperture, are investigated. The need for this study arises as it is one of the important peculiar limitations that stands in the way of achieving maximum range of transmission of acoustic signals. Application of the modified array format for the generation of narrow beam low frequency sound waves, through nonlinear interactions, is discussed. Other techniques that can be advantageously exploited in array synthesis are also investigated

Conversor inversor integrado três estados buck-boost para geração distribuída, com operação conectada ou ilhada

Pós-graduação em Engenharia Elétrica - FEIS

A dual resonance, image -guided, volume localization technique for magnetic resonance spectroscopy

An interleaved, dual resonance, volume localization technique for $\sp1$H/$\sp{31}$P magnetic resonance spectroscopy has been designed, implemented on a 2 T imager/spectrometer, and verified with phantom studies.^ Localization techniques, including several single voxel techniques and spectroscopic imaging, were implemented, and studies were performed to compare the efficiency of each sequence of $\sp1$H/$\sp{31}$P spectral acquisitions. The sequence chosen was a hybrid of the stimulated echo single voxel technique and the spectroscopic imaging technique.^ Water suppression during the $\sp1$H spectral acquisitions was accomplished by the use of three narrow bandwidth RF saturation pulses in combination with three spoiler gradients. The spoiler gradient amplitudes were selected on the basis of a numerical solution of the Bloch equations. A post-acquisition water suppression algorithm was used to minimize any residual water signal.^ For interleaved $\sp1$H/$\sp{31}$P acquisitions, a dual resonance RF coil was constructed and interfaced to the existing RF detection system via a custom-designed dual resonance transcoupler and switching system. Programmable attenuators were incorporated to allow for changes in receiver and transmitter attenuation "on the fly".^ To provide the rapidly switched gradient fields required for the $\sp1$H/$\sp{31}$P acquisitions, an actively screened gradient coil system was designed and implemented. With this system, gradient field rise times on the order of 100 $\mu$s were obtained. These rapid switching times were necessary for minimizing intrasequence delays and for improving localization quality and water suppression efficiency.^ The interleaved $\sp1$H/$\sp{31}$P volume localization technique was tested using a two-compartment phantom. Analysis of the data showed that the spectral contamination was less than three percent. One-to-one spatial correspondence of the $\sp1$H and $\sp{31}$P spectra was verified and allowed for direct correlation of the spectral data with a standard magnetic resonance image. ^

Plataformas experimentales para la formación en el área de la electrónica en entornos de e-learning

El campo de estudio relacionado con los laboratorios remotos en el ámbito educativo de las ciencias y la ingeniería está sufriendo una notable expansión ante la necesidad de adaptar los procesos de aprendizaje en dichas áreas a las características y posibilidades de la formación online. Muchos de los recursos educativos basados en esta tecnología, existentes en la actualidad, presentan ciertas limitaciones que impiden alcanzar las competencias que se deben adquirir en los laboratorios de ingeniería. Estas limitaciones están relacionadas con diferentes aspectos de carácter técnico y formativo. A nivel técnico las limitaciones principales se centran en el grado de versatilidad que son capaces de proporcionar comparado con el que se dispone en un laboratorio tradicional y en el modo de interacción del usuario, que provoca que el estudiante no distinga claramente si está realizando acciones sobre sistemas reales o simulaciones. A nivel formativo las limitaciones detectadas son relevantes para poder alcanzar un aprendizaje significativo. En concreto están relacionadas principalmente con un escaso sentimiento de inmersión, una reducida sensación de realismo respecto a las operaciones que se realizan o la limitada posibilidad de realizar actividades de forma colaborativa. La aparición de nuevas tecnologías basadas en entornos inmersivos, unida a los avances producidos relacionados con el aumento de la capacidad gráfica de los ordenadores y del ancho de banda de acceso a Internet, han hecho factible que las limitaciones comentadas anteriormente puedan ser superadas gracias al desarrollo de nuevos recursos de aprendizaje surgidos de la fusión de laboratorios remotos y mundos virtuales 3D. Esta tesis doctoral aborda un trabajo de investigación centrado en proponer un modelo de plataformas experimentales, basado en la fusión de las dos tecnologías mencionadas, que permita generar recursos educativos online que faciliten la adquisición de competencias prácticas similares a las que se consiguen en un laboratorio tradicional vinculado a la enseñanza de la electrónica. El campo de aplicación en el que se ha focalizado el trabajo realizado se ha centrado en el área de la electrónica aunque los resultados de la investigación realizada se podrían adaptar fácilmente a otras disciplinas de la ingeniería. Fruto del trabajo realizado en esta tesis es el desarrollo de la plataforma eLab3D, basada en el modelo de plataformas experimentales propuesto, y la realización de dos estudios empíricos llevados a cabo con estudiantes de grado en ingeniería, muy demandados por la comunidad investigadora. Por un lado, la plataforma eLab3D, que permite llevar a cabo de forma remota actividades prácticas relacionadas con el diseño, montaje y prueba de circuitos electrónicos analógicos, aporta como novedad un dispositivo hardware basado en un sistema de conmutación distribuido. Dicho sistema proporciona un nivel de versatilidad muy elevado, a nivel de configuración de circuitos y selección de puntos de medida, que hace posible la realización de acciones similares a las que se llevan a cabo en los laboratorios presenciales. Por otra parte, los estudios empíricos realizados, que comparaban la eficacia educativa de una metodología de aprendizaje online, basada en el uso de la plataforma eLab3D, con la conseguida siguiendo una metodología clásica en los laboratorios tradicionales, mostraron que no se detectaron diferencias significativas en el grado de adquisición de los resultados de aprendizaje entre los estudiantes que utilizaron la plataforma eLab3D y los que asistieron a los laboratorios presenciales. Por último, hay que destacar dos aspectos relevantes relacionados directamente con esta tesis. En primer lugar, los resultados obtenidos en las experiencias educativas llevadas a cabo junto a valoraciones obtenidas por el profesorado que ha colaborado en las mismas han sido decisivos para que la plataforma eLab3D se haya integrado como recurso complementario de aprendizaje en titulaciones de grado de ingeniería de la Universidad Politécnica de Madrid. En segundo lugar, el modelo de plataformas experimentales que se ha propuesto en esta tesis, analizado por investigadores vinculados a proyectos en el ámbito de la fusión nuclear, ha sido tomado como referencia para generar nuevas herramientas de formación en dicho campo. ABSTRACT The field of study of remote laboratories in sciences and engineering educational disciplines is undergoing a remarkable expansion given the need to adapt the learning processes in the aforementioned areas to the characteristics and possibilities of online education. Several of the current educational resources based on this technology have certain limitations that prevent from reaching the required competencies in engineering laboratories. These limitations are related to different aspects of technical and educational nature. At the technical level, they are centered on the degree of versatility they are able to provide compared to a traditional laboratory and in the way the user interacts with them, which causes the student to not clearly distinguish if actions are being performed over real systems or over simulations. At the educational level, the detected limitations are relevant in order to reach a meaningful learning. In particular, they are mainly related to a scarce immersion feeling, a reduced realism sense regarding the operations performed or the limited possibility to carry out activities in a collaborative way. The appearance of new technologies based on immersive environments, together with the advances in graphical computer capabilities and Internet bandwidth access, have made the previous limitations feasible to be overcome thanks to the development of new learning resources that arise from merging remote laboratories and 3D virtual worlds. This PhD thesis tackles a research work focused on the proposal of an experimental platform model, based on the fusion of both mentioned technologies, which allows for generating online educational resources that facilitate the acquisition of practical competencies similar to those obtained in a traditional electronics laboratory. The application field, in which this work is focused, is electronics, although the research results could be easily adapted to other engineering disciplines. A result of this work is the development of eLab3D platform, based on the experimental platform model proposed, and the realization of two empirical studies with undergraduate students, highly demanded by research community. On one side, eLab3D platform, which allows to accomplish remote practical activities related to the design, assembling and test of analog electronic circuits, provides, as an original contribution, a hardware device based on a distributed switching system. This system offers a high level of versatility, both at the circuit configuration level and at the selection of measurement points, which allows for doing similar actions to those conducted in hands-on laboratories. On the other side, the empirical studies carried out, which compare the educational efficiency of an online learning methodology based on the use of eLab3D platform with that obtained following a classical methodology in traditional laboratories, shows that no significant differences in the acquired degree of learning outcomes among the students that used eLab3D platform and those that attended hands-on laboratories were detected. Finally, it is important to highlight two relevant aspects directly related with this thesis work. First of all, the results obtained in the educational experiences conducted, along with the assessment from the faculty that has collaborated in them, have been decisive to integrate eLab3D platform as a supplementary learning resource in engineering degrees at Universidad Politecnica de Madrid. Secondly, the experimental platform model originally proposed in this thesis, which has been analysed by nuclear fusion researchers, has been taken as a reference to generate new educational tools in that field.

Sistema de conmutación y control de llamadas basado en OpenBTS y Asterisk

El presente trabajo empleó herramientas de hardware y software de licencia libre para el establecimiento de una estación base celular (BTS) de bajo costo y fácil implementación. Partiendo de conceptos técnicos que facilitan la instalación del sistema OpenBTS y empleando el hardware USRP N210 (Universal Software Radio Peripheral) permitieron desplegar una red análoga al estándar de telefonía móvil (GSM). Usando los teléfonos móviles como extensiones SIP (Session Initiation Protocol) desde Asterisk, logrando ejecutar llamadas entre los terminales, mensajes de texto (SMS), llamadas desde un terminal OpenBTS hacia otra operadora móvil, entre otros servicios.

Fluoxetine and norfluoxetine analysis by direct injection of human plasma in a column switching liquid chromatographic system

A column switching LC method is presented for the analysis of fluoxetine (FLU) and norfluoxetine (NFLU) by direct injection of human plasma using a lab-made restricted access media (RAM) column. A RAM-BSA-octadecyl silica (C-18) column (40 min x 4.6 mm, 10 mu m) is evaluated in both backflush and foreflush elution modes and coupled with a C-18 lab-made (50 mm x 4.6 mm, 3 pm) analytical column in order to perform online sample preparation. Direct injection of 100 mu L, of plasma samples is possible with the developed approach. In addition, reduction of sample handling is obtained when compared with traditional liquid-liquid extraction (LLE) and SPE. The total analysis time is around 20 min. A LOQ of 15 ng/mL is achieved in a concentration range of 15-500 ng/mL, allowing the therapeutic drug monitoring of clinical samples. The precision values achieved are lower than 15% for all the evaluated points with adequate recovery and accuracy. Furthermore, no matrix interferences are found in the analysis and the proposed method shows to be an adequate alternative for analysis of FLU in plasma.

Switching-off in a minimal time a fitzhugh-nagumo system

This paper deals with a system that describes an electrical circuitcomposed by a linear system coupled to a nonlinear one involving a tunneldiode in a flush-and-fill circuit. One of the most comprehensive models for thiskind of circuits was introduced by R. Fitzhugh in 1961, when taking on carebiological tasks. The equation has in its phase plane only two periodic solutions,namely, the unstable singular point S0 and the stable cycle Γ. If the system isat rest on S0, the natural flow of orbits seeks to switch-on the process by going- as time goes by - toward its steady-state, Γ. By using suitable controls it ispossible to reverse such natural tendency going in a minimal time from Γ toS0, switching-off in this way the system. To achieve this goal it is mandatorya minimal enough strength on controls. These facts will be shown by means ofconsiderations on the null control sets in the process.

The phasevarion: A genetic system controlling coordinated, random switching of expression of multiple genes

Several host-adapted bacterial pathogens contain methyltransferases associated with type III restriction-modification (R-M) systems that are subject to reversible, high-frequency on/off switching of expression (phase variation). To investigate the role of phase-variable expression of R-M systems, we made a mutant strain lacking the methyltransferase (mod) associated with a type III R-M system of Haemophilus influenzae and analyzed its phenotype. By microarray analysis, we identified a number of genes that were either up- or down-regulated in the mod mutant strain. This system reports the coordinated random switching of a set of genes in a bacterial pathogen and may represent a widely used mechanism.

Optimum switching point assessment of parallel braking resistor and serial current limiter for power system stability enhancement

A new control algorithm using parallel braking resistor (BR) and serial fault current limiter (FCL) for power system transient stability enhancement is presented in this paper. The proposed control algorithm can prevent transient instability during first swing by immediately taking away the transient energy gained in faulted period. It can also reduce generator oscillation time and efficiently make system back to the post-fault equilibrium. The algorithm is based on a new system energy function based method to choose optimal switching point. The parallel BR and serial FCL resistor can be switched at the calculated optimal point to get the best control result. This method allows optimum dissipation of the transient energy caused by disturbance so to make system back to equilibrium in minimum time. Case studies are given to verify the efficiency and effectiveness of this new control algorithm.

Volatility changes caused by the trading system:a Markov switching application

An expanding literature exists to suggest that the trading mechanism can influence the volatility of security returns. This study adds to this literature by examining the impact that the introduction of SETS, on the London Stock Exchange, had on the volatility of security returns. Using a Markov switching regime change model security volatility is categorized as being in a regime of either high or low volatility. It is shown that prior to the introduction of SETS securities tended to be in a low volatility regime. At the time SETS was introduced securities moved to a high volatility regime. This suggests that volatility increased when SETS was introduced.

Long-range automaton models of earthquakes: Power-law accelerations, correlation evolution, and mode-switching

We introduce a conceptual model for the in-plane physics of an earthquake fault. The model employs cellular automaton techniques to simulate tectonic loading, earthquake rupture, and strain redistribution. The impact of a hypothetical crustal elastodynamic Green's function is approximated by a long-range strain redistribution law with a r(-p) dependance. We investigate the influence of the effective elastodynamic interaction range upon the dynamical behaviour of the model by conducting experiments with different values of the exponent (p). The results indicate that this model has two distinct, stable modes of behaviour. The first mode produces a characteristic earthquake distribution with moderate to large events preceeded by an interval of time in which the rate of energy release accelerates. A correlation function analysis reveals that accelerating sequences are associated with a systematic, global evolution of strain energy correlations within the system. The second stable mode produces Gutenberg-Richter statistics, with near-linear energy release and no significant global correlation evolution. A model with effectively short-range interactions preferentially displays Gutenberg-Richter behaviour. However, models with long-range interactions appear to switch between the characteristic and GR modes. As the range of elastodynamic interactions is increased, characteristic behaviour begins to dominate GR behaviour. These models demonstrate that evolution of strain energy correlations may occur within systems with a fixed elastodynamic interaction range. Supposing that similar mode-switching dynamical behaviour occurs within earthquake faults then intermediate-term forecasting of large earthquakes may be feasible for some earthquakes but not for others, in alignment with certain empirical seismological observations. Further numerical investigation of dynamical models of this type may lead to advances in earthquake forecasting research and theoretical seismology.

Control system for actuation and sensing in digital microfluidics devices

Digital Microfluidics (DMF) is a second generation technique, derived from the conventional microfluidics that instead of using continuous liquid fluxes, it uses only individual droplets driven by external electric signals. In this thesis a new DMF control/sensing system for visualization, droplet control (movement, dispensing, merging and splitting) and real time impedance measurement have been developed. The software for the proposed system was implemented in MATLAB with a graphical user interface. An Arduino was used as control board and dedicated circuits for voltage switching and contacts were designed and implemented in printed circuit boards. A high resolution camera was integrated for visualization. In our new approach, the DMF chips are driven by a dual-tone signal where the sum of two independent ac signals (one for droplet operations and the other for impedance sensing) is applied to the electrodes, and afterwards independently evaluated by a lock-in amplifier. With this new approach we were able to choose the appropriated amplitudes and frequencies for the different proposes (actuation and sensing). The measurements made were used to evaluate the real time droplet impedance enabling the knowledge of its position and velocity. This new approach opens new possibilities for impedance sensing and feedback control in DMF devices.

Implementation and comparison of different switching techniques for shunt active power filters

This paper presents a comparison between three switching techniques that can be used in three-phase four-wire Shunt Active Power Filters (SAPFs). The implemented switching techniques are: Periodic-Sampling (PS), Triangular Carrier Pulse-Width Modulation (TC-PWM) and Space Vector PWM (SVPWM). The comparison between them is made in terms of the compensated currents THD%, implementation complexity, necessary CPU time and SAPF efficiency. To perform this comparison are presented and analyzed several experimental results, obtained with a 20 kVA Shunt Active Power Filter prototype, specially developed for this purpose. The control system of the developed SAPF is based in the p-q Theory with a grid synchronization algorithm p-PLL.

Reverse-transcriptase-associated RNaseH activity mediates template switching during reverse transcription in vitro.

During the first steps of reverse transcription of the retroviral genome, sequences present at the extremities of the RNA are used to reconstitute a host cell PolII promoter. The assembly of the promoter occurs by template switching, which takes advantage of a direct repeat at the ends of the RNA molecule. These steps are catalysed by the viral reverse transcriptase, which carries an intrinsic RNaseH activity that is probably also involved therein. To study the role of the RNaseH activity in this first template-switching event, an in vitro system has been developed based on primer extensions of synthetic RNAs. When an RNA was reverse transcribed with wild-type reverse transcriptase in the presence of a second RNA the 3' part of which was repeated at the 5' end of the first one, extension products could be observed corresponding to a chimeric cDNA comprising both RNA species. This template switching could not be detected when a mutant reverse transcriptase lacking the RNaseH activity was used. The results show that the RNaseH activity is needed to remove the 5' RNA sequences from the cDNA:RNA hybrid thereby enabling its translocation to another RNA containing an appropriate complementary target sequence.